Efficacy and safety of multiple treatments for small hepatocellular carcinoma: an updated systematic review and component network meta analysis
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Published on: September 30, 2021
Peiyan Sun1, Jianlin Wu1, Dong Cai1
1Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Background:
This is an updated component network meta-analysis to evaluate efficacy and safety of various therapeutic approaches and their combinations for small hepatocellular carcinoma (SHCC) following PRISMA 2020 guideline.
Methods:
We screened two previously published meta-analyses on this topic, and searched PubMed, Embase, and the Cochrane Library from 1 January 2021 to 12 March 2026 for randomized controlled trials (RCTs) focusing on treatments of SHCC. We compared the efficacy and safety of surgical resection (SR), radiofrequency ablation (RFA), microwave ablation (MWA), transcatheter arterial chemoembolization (TACE), radiotherapy (RT), and their combinations. Outcomes were overall survival (OS), recurrence-free survival (RFS), and the rate of complications. Standard network meta-analysis (NMA), component NMA were performed, adding subgroup analysis, network meta-regression, and meta-regression between outcomes for sensitive analysis. This study is registered in PROSPERO (CRD420251132447).
Findings:
We included 41 RCTs involving 5804 patients. RFA + 125I [OS: Hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.81; RFS: HR 0.51, 95% CI 0.32-0.81], TACE + RFA (OS: HR 0.66, 95% CI 0.52-0.85; RFS: HR 0.70, 95% CI 0.57-0.86), TACE + SR (OS: HR 0.30, 95% CI 0.16-0.58; RFS: HR 0.37, 95% CI 0.23-0.59) and SR (OS: HR 0.83, 95% CI 0.71-0.98; RFS: HR 0.82, 95% CI 0.71-0.94) had better OS and RFS than RFA; MWA had better RFS (HR 0.75, 95% CI 0.60-0.93), while TACE + RT might worsen RFS (HR 3.53, 95% CI 1.29-9.62). SR yielded more complications (RR 1.52, 95% CI 1.14-2.03). Better liver function (Child-Pugh A) was negatively correlated with HR of RFS (-0.16, 95% CI -0.28 to -0.04).
Interpretation:
SR remains the foundational treatment for SHCC, and TACE + SR exhibits superior efficacy in SHCC patients. RFA + 125I serves as a potential alternative in patients with unresectable tumors, and most locoregional treatments show effects comparable to SR for SHCC. Liver function may negatively affect relative efficacy of treatments.
Funding:
This study is funded by 1.3.5 project for disciplines of excellence-Clinical Research Incubation Project, West China Hospital, SCU; 1.3.5 project for Artificial Intelligence West China Hospital, SCU; National Natural Science Foundation of China for Young Scientists Fund; Sichuan Science and Technology Program; (Qilu) Clinical Research of Sichuan Anticancer Association.
Insights
Surgical resection (SR) combined with transcatheter arterial chemoembolization (TACE) shows superior efficacy for small hepatocellular carcinoma (SHCC). Radiofrequency ablation (RFA) combined with iodine-125 implantation is a viable alternative for unresectable tumors.
Area of Science:
- Hepatobiliary Malignancies
- Oncologic Therapies
- Evidence Synthesis
Background:
- Small hepatocellular carcinoma (SHCC) presents unique treatment challenges.
- Evaluating diverse therapeutic strategies, including combinations, is crucial for optimizing SHCC management.
- Previous meta-analyses provide a foundation, necessitating updated evidence synthesis.
Purpose of the Study:
- To conduct an updated component network meta-analysis evaluating the efficacy and safety of various treatments for SHCC.
- To compare surgical resection (SR), radiofrequency ablation (RFA), microwave ablation (MWA), transcatheter arterial chemoembolization (TACE), radiotherapy (RT), and their combinations.
- To assess overall survival (OS), recurrence-free survival (RFS), and complication rates.
Main Methods:
- Systematic literature search of PubMed, Embase, and Cochrane Library (Jan 2021-Mar 2026) for randomized controlled trials (RCTs).
- Inclusion of 41 RCTs with 5804 patients.
- Application of standard and component network meta-analysis (NMA), incorporating subgroup and meta-regression analyses.
Main Results:
- Combinations of TACE + SR (OS: HR 0.30, RFS: HR 0.37) and RFA + 125I (OS: HR 0.50, RFS: HR 0.51) demonstrated superior OS and RFS compared to RFA alone.
- SR (OS: HR 0.83, RFS: HR 0.82) and MWA (RFS: HR 0.75) also showed improved RFS over RFA.
- SR was associated with a higher complication rate (RR 1.52); better liver function (Child-Pugh A) correlated with poorer RFS.
Conclusions:
- TACE + SR is a highly effective treatment for SHCC.
- RFA + 125I offers a promising alternative for unresectable SHCC.
- Most locoregional therapies show comparable efficacy to SR, with liver function impacting treatment outcomes.
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